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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
171

The effects of Taurine depletion on rat heart electrophysiology /

De Roode, Michael R. January 1989 (has links)
Taurine is an amino acid found in high concentration (20-30 mM) in mammalian heart. Treatment of rats with the transport antagonist guanidinoethyl sulfonate (GES) depletes cardiac taurine ($>$70%). Electrocardiograms were recorded weekly in restrained unanaesthetized rats. GES treatment caused a selective prolongation of the QT interval which was correlated with the degree of myocardial taurine depletion (r$ sp2$ = 0.92, p $<$ 0.001). Ventricular muscle action potential durations (APD$ sb{95}$) from taurine-depleted hearts were significantly prolonged compared to control (88 +/- 8 ms vs. 66 +/- 9 ms; p $<$ 0.001). Taurine supplements given to depleted rats reversed the taurine depletion and the QT prolongation; no effect was seen in controls. No action potential differences between control and "reversed" rats were seen. Superfusion of GES or taurine at concentrations of 0.2-10 mM had no effect on action potential characteristics of control or taurine-depleted hearts. When hamsters were GES-treated no cardiac biochemical or QT changes were seen.
172

Effects of Interleukin-3 on murine fetal hemopoiesis in utero

Delorme, Danielle January 1990 (has links)
The effect of interleukin-3 (IL-3), a candidate hemopoietic growth factor, on prenatal hemopoiesis is unclear. Microinjection of IL-3 directly into mouse fetuses (day 13) via the yolk sac, allowed us to evaluate the effects on morphogenetic events and more specifically on fetal liver populations using quantitative in vitro clonal assays for hemopoietic precursors. Control studies, required to distinguish stress effects of surgical laparotomy and microinjection, clearly revealed that the fetal liver is a sensitive organ responding with limited tissue disorganization, reduced cellularity and erythropoietic activity as identified 24 h after experimental intervention. Microinjection of 15 units of IL-3 promoted significant expansion of the depleted fetal liver hemopoietic cell populations and had stimulatory effects on connective tissue mast cells, absolute cell numbers including hemopoietic precursors (erythroid, granulocyte, macrophage, megakaryocyte) compared to controls. These studies suggest that fetal liver cells acquire a responsiveness to IL-3 early in development and that, IL-3 has a positive stimulatory effect on fetal liver cell populations, promoting the recovery of normal liver hemopoiesis.
173

Variations in the Hypothalamic-Pituitary-Adrenal response to stress during the estrous cycle in the rat

Viau, Victor January 1990 (has links)
To investigate the role of gonadal steroids in the hypothalamic-pituitary-adrenal (HPA) response to stress, we studied adrenocorticotrophin (ACTH) and corticosterone (B) responses to 20 min restraint stress in cycling female rats, and in ovariectomized (OVX) rats replaced with physiological levels of estradiol (E2) and progesterone (P). In cycling rats, we found significantly higher peak ACTH and B responses to stress during proestrous compared to the estrous and diestrous phases. No differences were found in either basal ACTH and B levels across the cycle phases. In a separate study, OVX rats were maintained on low, physiological levels of E2 and P with silastic implants for three days, and injected either with oil (O$ sp prime$), 10 ug of E2 (E$ sp prime$) 24 h before stress testing, or with E2 and 500 ug P 24 h and 4 h, respectively, prior to stress (EP$ sp prime$). These treatments mimicked endogenous profiles of E2 and P occurring during diestrous, proestrous, and late proestrous-early estrous phases, respectively. In response to stress, ACTH levels were higher in the E$ sp prime$ group compared to the EP$ sp prime$ and O$ sp prime$ groups. Within the 20 min stress period, ACTH levels and plasma B levels in the E$ sp prime$ group were significantly higher after the onset of stress, compared to the EP$ sp prime$ and O$ sp prime$ groups. $ beta$-endorphin-like immuno-reactive responses to restraint stress were also significantly higher in the E$ sp prime$ group. There was no effect of E2 on ACTH clearance. These results indicate that the HPA axis in the female rat is most sensitive to stress during proestrous.
174

Chloride channels in epithelia

Low, Wendy January 1993 (has links)
The outwardly rectifying chloride channel is found in most vertebrate cells however its physiological role is uncertain. Patch clamp, short-circuit current, and electronic cell sizing techniques were used to investigate the role of the outward rectifier in transepithelial chloride secretion and cell volume regulation, the two main functions that have been proposed for this channel in epithelia. Patch clamp studies of the human cell lines PANC-1 and T$ sb{84}$ showed that the chloride channel blockers IAA-94 and NPPB decrease the open probability of the outward rectifier, with half-maximal inhibition at 15 $ mu$M and 23 $ mu$M, respectively. At these concentrations the blockers did not affect cAMP-induced short-circuit current. They did inhibit the regulatory volume decrease (RVD) which occurs after hypotonic cell swelling, but only at much higher concentrations. Moreover, the commonly-used inhibitor DIDS, which blocks the outward rectifier in the 10-20 $ mu$M range, had no effect on the RVD when tested at 100 $ mu$M. The results indicate that the outwardly rectifying Cl channel does not mediate a significant fraction of transepithelial Cl secretion across T$ sb{84}$ cells. Although the data do not exclude a role for the outward rectifier in cell volume regulation, the selectivity and pharmacological properties of the swelling-induced anion conductance in T$ sb{84}$ cells is more similar to the ClC-2 channel than to the outward rectifier.
175

Differential secretion from prestored heterogeneous protein sources is the basis of regulated nonparallel digestive enzyme secretion by the exocrine pancreas

Miller, Paul E. January 1989 (has links)
For two decades, multiple observations of nonparallel pancreatic secretion, wherein digestive enzyme proportions change rapidly following various digestive stimuli, have conflicted with the concept of exocrine pancreatic homogeneity and the exocytosis model of parallel synthesis, transport and secretion of proteins. Evidence of pancreatic heterogeneity is presented, potentially resolving this longstanding controversy. Correlation and regression analysis simultaneously demonstrated exocytosis and nonparallel secretion, suggesting the existence of multiple heterogeneous exocytotic pathways. Next, heterogeneous prestored pancreatic protein sources were directly demonstrated using double isotopic labelling; temporal and secretagogue-specific regulation of the heterogeneous secretory sources was uncovered. Finally, specific enzyme proportions were linked to the heterogeneous sources by densitometric measurements of electrophoretic gels of secreted proteins. Thus, it appears that differential secretion from heterogeneous sources of prestored secretory proteins containing unique proportions of digestive enzymes is the basis of regulated nonparallel secretion in the exocrine pancreas.
176

Roles of substance P in the mediation or modulation of a nociceptive reflex in the rat

Cridland, Ruth Anne January 1987 (has links)
This thesis investigates the effects of substance P on a spinal nociceptive reflex in the rat. Intrathecal administration of substance P and other analogous peptides to the L5 vertebral level produced a dose-dependent decrease in reaction time to tail withdrawal from a noxious radiant heat source. Similar administration of VIP, galanin, CGRP, angiotensin II, somatostatin and TRH failed to mimic these effects of substance P. As substance P was found to equally decrease the reaction time in spinal transected rats, it is concluded that this facilitation occurs via a spinal mechanism alone. / Administration of substance P at the lower thoracic level increased reaction time. Evidence is provided to suggest that this increase in reaction time may involve the release of an opioid peptide into the circulation from the adrenal medullae. / Noxious cutaneous stimulation to the tail of anaesthetized rat produced a facilitation of the tail flick reflex which was similar to that induced by exogenous administration of substance P. This decrease in reaction time was attenuated by intrathecal administration of a substance P antagonist. / These results support an earlier hypothesis made by others that substance P may be involved in the transmission of nociceptive information in the spinal cord.
177

Central mechanisms responsible for generating respiratory-modulated sympathetic nerve discharge

Bachoo, Manjit January 1988 (has links)
The experimental work presented in this thesis explores, in anaesthetized and mid-collicular decerebrate, unanesthetized, cats, the properties of two components of the discharge of sympathetic nerves which are time-locked to the central respiratory cycle and are presumably generated within the central nervous system. One is the inspiration-synchronous burst, the other is a previously unknown late-expiratory burst. The properties of the inspiration-synchronous burst and its temporal relation to the phrenic nerve burst were studied under conditions in which the frequency of the latter was changed over a wide range by superior laryngeal nerve stimulation, by changes in ventilation frequency while the phrenic nerve burst was locked to the pump, and by hypocapnic hyperthermia. The data obtained are consistent with the hypothesis of a common rhythmic driver for phrenic motoneurons and sympathetic preganglionic neurons. Stimulation of low-threshold afferents in the superior laryngeal nerve selectively suppressed the phrenic burst together with the inspiration-synchronous sympathetic discharge and produced vasodilatation. The contribution of the inspiration-synchronous sympathetic discharge to neurogenic vasoconstriction was estimated, in the hindlimb of the cat, from the magnitude of the vasodilatation. A late-expiratory burst of sympathetic discharge was produced by systemic hypercapnia and by raising end-expiratory pressure to between 2 and 7 cmH$ sb2$O. Circumstantial evidence suggests this late-expiratory burst is due to input from late-expiratory neurons to sympathetic preganglionic neurons. As a background to the experimental data a survey is presented of present knowledge of the mechanisms providing mechanical and neural coupling between respiration and circulation. The functional significance of respiratory modulation of sympathetic activity is discussed.
178

The involvement of second messengers in hippocampal activity and seizure / / Muscarinic actions in hippocampus are probably not mediated by cycle GMP.

Agopyan, Nadia M. January 1990 (has links)
This thesis focusses on the seizure-promoting effects of second messengers, in particular calcium and others activated by calcium in CA1 subfield of rat hippocampus in situ and in vitro. Interictal discharges were simulated in hippocampal slices using the low Ca$ sp{2+}$ model where synaptic transmission is blocked. The antiepileptic drug valproic acid (VPA), which is postulated to potentiate GABAergic responses, reduced the low Ca$ sp{2+}$ field bursts, thereby suggesting a non-synaptic mechanism of action of VPA. Extracellular and intracellular recordings from hippocampal neurones bathed in low Ca$ sp{2+}$ solution revealed that even though evoked transmitter release was blocked, small spontaneous GABAergic release still persisted and that a voltage-dependent Cl conductance contributed to burst termination. To test the hypothesis that epileptiform activity induced by lowering extracellular Ca$ sp{2+}$ was in part due to an alteration in the delicate balance between intracellular messengers, I investigated the effects of Ca$ sp{2+}$ (a) on the activity of hippocampal neurones, and (b) on the second messengers activated by acetylcholine (ACh), a neuromodulator known for its seizure promoting effects. Inhibiting cyclic nucleotide-dependent kinase activity was H-8 did not have any effect either on excitability of CA1 neurones or the excitatory actions of ACh. Activation of protein kinase C (PKC), a Ca$ sp{2+}$-binding protein, by phorbol esters enhanced high threshold Ca$ sp{2+}$ currents and subsequently facilitated neurotransmitter release (both excitatory and inhibitory) without significantly affecting ACh-induced effects. Inhibition of PKC by several dual PKC and Ca$ sp{2+}$/calmodulin-dependent kinase antagonists, such as H-7, sphingosine, and trifluoroperazine reduced inhibitory transmission and prevented ACh-induced effects. / The evidence presented in this thesis was combined with that in the literature to propose a model accounting for the seizure-promoting effects of ACh: that gangliosides and/or sphingolipids are metabolized to sphingosine upon muscarinic receptor activation leading to inhibition of both PKC and Ca$ sp{2+}$/calmodulin-dependent kinases.
179

Investigations into the role of substance P and the NK-1 receptor in an animal model of neuropathic pain

Fallis, Brooks A. January 2002 (has links)
This study investigates the role of substance P and NK-1 receptors in an animal model of neuropathic pain. Unlike naive animals, innocuous peripheral stimulation of neuropathic animals was determined to cause heterosegmental inhibition in the tail-flick test as well as increased plasma extravasation in the paw. These effects were prevented by administration of CP-96,345 before stimulation. Additionally, CP-96,345 or an antisense oligonucleotide against NK-1 receptors significantly alleviated mechanical allodynia in neuropathic animals. Finally, mass spectrum of lumbar spinal cord of neuropathic but not naIve animals showed a significant upregulation of substance P. We conclude that innocuous stimulation of a neuropathic area could trigger activation of NK-1 receptors, presumably due to binding of substance P. Furthermore, this activation of NK-1 receptors could be central to the perception of mechanical allodynia in neuropathic pain. These results justify the investigation of inhibiting the interaction between substance P and the NK-1 receptor for the treatment of drug resistant neuropathies.
180

In vivo study of the physiological role of acylation stimulating protein in mice

Xia, Zhunan January 2002 (has links)
ASP acts as a paracrine and autocrine signal to increase triglyceride synthesis in adipocytes. ASP administration results in more rapid postprandial lipid clearance. This present work consists of a series of experiments on complement C3 knockout mice (therefore ASP deficient mice) in vivo. The aim of this work is to understand the role of Acylation stimulating protein (ASP) in energy regulation. / Compared to wild type mice, ASP deficient mice have delayed triglyceride and fatty acid clearance, decreased fat mass and body weight with concurrent increases in food intake. Both male and female ASP deficient mice have increased oxygen consumption, an indication of increased energy expenditure. This effect was not dependent on the presence of leptin. On the other hand, the mechanism of increased energy expenditure was different in male and female ASP deficient mice. Female ASP deficient mice have increased movement while the male ASP deficient mice were found to have increased uncoupling protein-3 expression in muscle. Fat load tests in the male mice demonstrate ASP deficiency redirects absorbed energy from storage in adipose tissues towards utilization in liver and muscle. Acute administration of ASP normalizes this process. / The results from these studies suggest that ASP is a key hormone regulating lipid storage in adipocytes. Deficiency of ASP leads to energy repartition, decreased energy storage and increased energy expenditure. In short, ASP deficiency results in obesity resistance.

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